Fibroblast growth factor receptor (FGFR) family (FGFR)

The fibroblast growth factor receptor (FGFR) family comprises four highly conserved transmembrane receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, and FGFR4) that play critical roles in regulating cell proliferation, differentiation, and survival (UniProt, 2024). Upon binding to their fibroblast growth factor (FGF) ligands and heparin sulfate proteoglycan co-receptors, FGFRs undergo dimerization and trans-autophosphorylation, triggering downstream signaling cascades such as the MAPK/ERK and PI3K/AKT pathways (Nature Reviews Cancer, 2021). Aberrant FGFR signaling, driven by gene amplifications, point mutations, or chromosomal translocations, is a well-documented oncogenic driver in various malignancies, including urothelial carcinoma, cholangiocarcinoma, and breast cancer (PubMed, 2022). Consequently, the FGFR family has become a significant therapeutic target, leading to the development of selective small-molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (FDA, 2024). While these therapies show clinical efficacy, they are often associated with unique class-effect toxicities, most notably hyperphosphatemia due to the inhibition of FGF23 signaling in the kidneys (StatPearls, 2023).

Other names

FGFR1FGFR2FGFR3FGFR4CD331CD332CD333CD334Fibroblast growth factor receptor 1-4

Small molecule inhibitors typically act as ATP-competitive inhibitors of the intracellular tyrosine kinase domain, while monoclonal antibodies block ligand binding or receptor dimerization (Nature Reviews Drug Discovery, 2019).